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European Journal of Integrative Medicine 4 (2012) e234–e244

Review article

Does acupuncture improve the outcome of in vitro fertilization? Guidance

for future trials
Fan Qu a,b,1 , Jue Zhou c,b,1 , Mark Bovey d , Giovanna Franconi e , Kelvin Chan f,g , Caroline Smith f ,
Dan Jiang h , Nicola Robinson i,∗
a Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, China
b School of Medicine, King’s College London, London SE5 9RJ, UK
c College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang 310012, China
d British Acupuncture Council, London W12 9HQ, UK
e Department of Systems Medicine, Tor Vergata University, Rome 00133, Italy
f Centre for Complementary Medicine Research, University of Western Sydney, Sydney, NSW 2751, Australia
g Faculty of Pharmacy, The University of Sydney, Sydney, NSW 2006, Australia
h Asante Academy of Chinese Medicine, Middlesex University, London N19 5LW, UK
i Faculty of Health and Social Care, London South Bank University, London SE1 0AA, UK

Received 31 May 2012; received in revised form 15 July 2012; accepted 26 July 2012

Abstract
Introduction: The comprehensive review was to appraise the current evidence from both randomized and non-randomized trials by using both
Chinese and western databases and to highlight the issues which could guide future trial design. Many infertile couples have chosen acupuncture as
an adjunct when they undergo in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment. More than forty trials have emerged
since the first clinical research published in 1999 explored the effects of acupuncture on the outcomes of IVF. However, the current evidence makes
it difficult for clinical practitioners and patients to make a decision on whether to choose acupuncture as an adjunct when undergoing IVF or ICSI
treatment.
Methodology: A total of thirty-three randomized and 5 non-randomized controlled trials were included in the review.
Results: Based on this comprehensive review and analysis of all the relevant trials, the authors identify the factors which have contributed to these
inconsistencies, and which should be considered in the design of future studies.
Discussion/conclusions: These items included in the review could provide useful recommendations and guidelines, which will in turn promote
better trial design and improve the evidence base for the use of acupuncture for IVF.
Crown Copyright © 2012 Published by Elsevier GmbH. Open access under CC BY license.

Keywords: Acupuncture; In vitro fertilization (IVF); Intracytoplasmic sperm injection (ICSI)

Introduction chosen acupuncture as an adjunct when they undergo IVF or

In vitro fertilization (IVF) is an effective treatment for vari-
ous causes of infertility, and has produced over 3,500,000 babies
worldwide [1]. In recent years, many infertile couples have
∗ Corresponding author at: Traditional Chinese Medicine (TCM) and Inte-
grated Health, Faculty of Health and Social Care, London South Bank University,
103 Borough Road, London SE1 0AA, UK. Tel.: +44 0207815 7940;
fax: +44 0207815 8490.
E-mail addresses: nicky.robinson@lsbu.ac.uk, syqufan@zju.edu.cn,
fan.qu@kcl.ac.uk (N. Robinson).
1 Both authors contributed equally to the study.
intracytoplasmic sperm injection (ICSI) [2–8]. However, the
current evidence makes it difficult for clinical practitioners and
patients to make a decision on whether to choose acupuncture as
an adjunct when undergoing IVF or ICSI treatment [9]. Since the
first clinical research exploring the effects of acupuncture on the
outcomes of IVF was published in 1999 [10], more than forty
trials have emerged. However, the conclusions of these trials
have been inconsistent. A recent review concluded that acupunc-
ture can improve the outcome of IVF and the mechanisms may
be related to the increased uterine blood flow, inhibited uter-
ine motility, and the decreased levels of depression, anxiety and
stress [11]. Three systematic reviews or meta-analysis designed

1876-3820 Crown Copyright © 2012 Published by Elsevier GmbH. Open access under CC BY license.
http://dx.doi.org/10.1016/j.eujim.2012.07.978
 F. Qu et al. / European Journal of Integrative Medicine 4 (2012) e234–e244
to explore the effects of acupuncture on IVF outcomes published
in 2008 [2–4] also showed that acupuncture improved rates of
pregnancy or live birth in women undergoing IVF treatment. A
systematic review and meta-analysis reviewed studies that did
not include the Streitberger needle as a control and it demon-
strated that acupuncture improved clinical pregnancy rate (CPR)
and live birth rate (LBR) among women undergoing IVF [8].
However, another meta-analysis [7] together with its updated
version [5] did not find any improvement in IVF outcomes fol-
lowing acupuncture, nor did Cheong’s updated review in 2010
[6]. Since the publication of these reviews further randomized
controlled trials have been published. A large, randomized, mul-
ticentre, double-blinded and placebo-controlled trial including
635 women undergoing IVF or ICSI published in 2010 also
failed to show that acupuncture administered in relation to
embryo transfer (ET) has effects on the outcomes of IVF or
ICSI [12]. The investigators achieved complete follow-up of all
pregnancies and obtained outcomes relating to the number of
live births, which is considered to be the optimal endpoint for
assisted reproduction treatment. Another large, prospective, ran-
domized, single-center, single-blinded and placebo-controlled
trial including 309 women undergoing IVF or ICSI published
in 2011 showed that electro-acupuncture administered before
and after ET significantly improved the clinical outcomes of
IVF [13]. The primary outcome was CPR, and secondary out-
comes were biochemical pregnancy rate (BCPR), implantation
rate (IR), miscarriage rate (MR), and LBR. This evidence raises
questions regarding how research in this area was conducted
and how future research in this area should be carried out. High
quality of evidence is needed before any specific intervention is
incorporated into routine clinical practice [14] even though prac-
titioners and patients report its success as a supportive treatment.
In our systematic review with meta-analysis of 17 randomized
controlled trials of acupuncture during IVF or ICSI treatment
on the outcomes of IVF or ICSI, found no significant benefits
for the use of acupuncture for a variety of outcomes [15]. It is
possible a consensus amongst experts on key components of a
best practice treatment protocol can be achieved, although there
exists a lack of homogeneity in the research and clinical litera-
ture on assisted reproductive technology (ART) and acupuncture
[16]. The aim of this comprehensive review was to appraise the
current evidence from both randomized and non-randomized tri-
als by using both Chinese and western databases which could
inform and provide guidance for future trial design.
Methods
To review the existing studies regarding acupuncture as an
adjunct therapy for IVF, a systematic literature search was per-
formed using MEDLINE (1966 to January 2012), SCISEARCH
(1974 to January 2012), Cumulative Index to Nursing and Allied
Health Literature (1982 to January 2012), the Cochrane Men-
strual Disorders and Subfertility Group trials register (January
2012), AMED (Allied and Complementary Medicine) (1985
to January 2012), EMBASE (1974 to January 2012), Wan-
fang Database (1982 to January 2012), China Academic Journal
Electronic full text Database in China National Knowledge
e235
Infrastructure (1982 to January 2012), Index to Chinese Period-
ical Literature (1978 to January 2012) and ISI Proceedings for
conference abstracts, and ISRCTN Register and meta-register
for randomized controlled trials (mRCT). The reference lists of
relevant primary and review articles were examined to identify
cited articles not captured by electronic searches.
Search terms or key words included “acupuncture”,
“acupressure”, “moxibustion”, “electro-acupuncture”,
“auricular-acupuncture”, “laser acupuncture”, “auricu-
lotherapy”, “acupuncture therapy” “transcutaneous electrical
acupoint stimulation”, and “Traditional Chinese Medicine” “in
vitro fertilization”, “fertilization in vitro”, “intracytoplasmic-
sperm-injection”, “assisted reproductive techniques”, “assisted
reproduction treatment”, “oocytes”, “egg collection”, “embryo
transfer” and “embryo implantation”.
The acupuncture intervention included any accepted regi-
men of acupuncture including traditional needling acupuncture,
auricular acupuncture, electro-acupuncture and laser acupunc-
ture. Studies using Chinese herbs in conjunction with
acupuncture were also included in this review. As the focus of
the review was on whether acupuncture improves the outcomes
of IVF or not, studies were only included from which exact data
could be extracted on at least one of the following outcomes:
CPR, BCPR, ongoing pregnancy rate (OPR), IR, LBR and MR.
No restrictions of language or publication type were placed in
the review. Five trials [17–21] were excluded due to lack of
exact data on IVF outcomes or inconsistent data on the number
of canceled IVF cycles. Data abstracted from the accepted arti-
cles included: details of the participants, countries, intervention,
IVF outcomes, randomization, single/multi-center, concealment
of allocation, control and placebo intervention, blinding, com-
parability at baseline, acupuncture practitioner and adherence to
standards for reporting interventions in clinical trials of acupunc-
ture (STRICTA) [22].
Results and discussion
A total of thirty-three randomized and 5 non-randomized con-
trolled trials were included. The summary of the characteristics
of the included studies identified and the quality evaluation of
the studies are shown in Tables 1 and 2 respectively. Compared
with our previous systematic review and meta-analysis [15], 16
additional randomized and 5 non-randomized controlled trials
were included in this comprehensive review. The objective of the
previous systematic review was to explore whether acupuncture
can improve the outcomes of IVF or ICSI [15], This compre-
hensive review was to appraise the current evidence from both
randomized and non-randomized trials to inform and provide
guidance for future trial design. As our systematic review with
meta-analysis was completed in October 2010, the new research
published after that date had not been included [15], however,
this comprehensive review includes all of these new papers. By
investigating the individual studies identified and the differences
in these studies, the authors highlight the factors which may
have contributed to the variability of the results as seen in previ-
ous meta-analyses [2–8], and which should be considered in the
design of future studies. The key factors identified which may
e236 F. Qu et al. / European Journal of Integrative Medicine 4 (2012) e234–e244

Table 1
Summary of the studies.
Study Participants Country Intervention Control IVF outcomes

Stener-Victorin 150 randomized—no inclusion Sweden EA and PCB Alfentanil + PCB CPR, IR, MR
et al. [9] criteria
Paulus et al. [27] 160 randomized—only women with Germany TA and AA for 25 min Lying still for CPR, OPR, LBR
good quality embryos included before and after ET 25 min before and
after ET
Balk et al. [34] 10 Non-randomized—women U.S.A. TA No intervention CPR,
undergoing IVF
Paulus et al. [28] 200 randomized—only women with Germany TA for 25 min before and Sham CPR, OPR, LBR
good quality embryos included after ET (noninvasive)
acupuncture
Stener-Victorin 286 randomized—eligible women Sweden PCB and EA Alfentanil + PCB CPR, OPR, IR,
et al. [22] aged <38 years, BMI <28 kg/m2 , had MR
four or more follicles of size 18 mm
or more and no more than three
previous IVF attempts
Zhang et al. [46] 210 randomized—only women with China TA for 25 min before and Sham CPR
good quality embryos included after ET (noninvasive)
acupuncture
Humaidan and 200 randomized—no inclusion Denmark PCB and EA Alfentanil + PCB CPR, BCP, IR
Stener-Victorin criteria;
[23]
Gejervall et al. 160 randomized—no inclusion Sweden PCB and EA Premedication + alfentanilCPR
+ PCB
[24] criteria
Benson et al. [35] 258 randomized—women scheduled U.S.A. Traditional needle or Sham laser CPR, BCPR
to have ET were eligible Laser acupuncture for acupuncture,
25 min before and after relaxation or no
ET intervention
Dieterle et al. [29] 225 randomized—no inclusion Germany TA for 30 min after ET Placebo needling CPR, BCPR,
criteria and 3 days later + Chinese at acupoints OPR, IR, LBR,
medical herbs designed not to MR
influence fertility
Domar et al. [36] 83 randomized—women scheduled U.S.A. TA and AA for 25 min Lying still for CPR
to undergo ET from a fresh cycle before and after ET 25 min before and
using their own eggs after ET
Humaidan et al. 152 randomized—women Denmark TA and EA TA and EA CPR
[26] undergoing IVF
Sator- 94 randomized—women aged <43 Austria AA with or without PCA + placebo CPR
Katzenschlager years, BMI <28 kg/m2 , had four or electrical AA
et al. [25] more follicles of size >18 mm stimulation + PCA
Smith et al. [32] 228 randomized—women with a Australia TA Placebo needling CPR, OPR
planned ET were eligible at points close to
the real
acupuncture
acupoints
Westergaard et al. 300 randomized—no inclusion Denmark TA for 25 min before and Bed rest for 1 h CPR, BCPR,
[30] criteria after ET with or without a after ET OPR, IR, LBR
third session for 25 min 2
days after ET
Xu [47] 57 randomized—no inclusion criteria China TA and Chinese No intervention CPR
medicinal herbs
Craig et al. [37] 107 randomized—women U.S.A. TA for 25 min before and No intervention CPR, BCPR
undergoing IVF who have not had after ET
acupuncture within 3 months
Cui et al. [48] 94 randomized—women undergoing China TA before and during No intervention CPR,
IVF who had a normal uterine cavity COH
shown on ultrasound scanning and
had no history of COH
Cai et al. [38] 126 Non-randomized The women U.S.A. TA, AA and Chinese TA, AA and CPR, LBR
were divided into 3 groups based on medicinal herbs Chinese medicinal
the ages herbs
Group A: <35 years old
Group B: between 35 and 39 years
old
Group C: >39 years old
 F. Qu et al. / European Journal of Integrative Medicine 4 (2012) e234–e244 e237

Table 1 (Continued)
Study Participants Country Intervention Control IVF outcomes

Cui et al. [49] 126 Non-randomized—The women China EA EA CPR, IR

were divided into 3 groups based on
the diagnosis of the patient’s
syndrome according to TCM theory:
Group A: Kidney deficiency type
Group B: Liver-qi stagnation type
Group C: Phlegm dampness type
Fratterelli et al. 1000 randomized—women receiving U.S.A. Traditional needle or Sham laser CPR, BCPR,
[39] an ET Laser acupuncture acupuncture, OPR, IR
relaxation or no
intervention
Chen et al. [50] 60 randomized—women with poor China TA around ovulation No intervention CPR, IR, MR
ovarian response or decreased reserve induction
Chen et al. [51] 100 randomized—women China EA from the 5th day of No intervention CPR, IR
undergoing frozen ET natural menstrual cycle
Domar et al. [40] 150 randomized—women scheduled U.S.A. TA for 25 min before and Lay quietly for CPR, BCPR
to have ET using non-donor eggs after ET same amounts of
were eligible time
Ho et al. [52] 44 randomized—women had to China EA was performed four No intervention CPR,
consent to be randomly assigned to times, twice a week for 2
one of the two groups weeks, from day 2 of the
study to the day before
TVOR
Kong et al. [41] 52 randomized—women between 29 U.S.A. TA and EA 1. TA CRP
and 45 years old, undergoing IVF 2. EA
Magarelli et al. 67 Non-randomized—women U.S.A. EA No intervention CPR, IR, LBR,
[42] undergoing IVF, agreeing to have a MR
vial of blood drawn during the
normal standard times (7 A.M. to
9 A.M.)
Smith et al. [33] 28 randomized—women undergoing Australia TA and AA No intervention BCPR
an IVF cycle with a planned ET at
day 3 or day 5
So et al. [53] 370 randomized—women who had a China TA for 25 min before and Placebo needling CPR, BCPR,
normal uterine cavity shown on after ET for 25 min before OPR, IR, LBR,
ultrasound scanning on the day of and after ET MR
TVOR
Andersen et al. 635 randomized—<37 years of age, Denmark TA accompanying ET Placebo needling CPR, BCPR,
[11] treatment with IVF/ICSI and transfer accompanying ET OPR, LBR
of one or two embryos in the first,
second or third stimulated cycle
Arnoldi et al. [31] 204 randomized—women for Italy TA No intervention CPR, IR
IVF-ICSI with an unfavorable
reproductive prognosis were assigned
randomly to two groups. Inclusion
criteria were as follow: (1) at least
two previous poor responses to
ovarian stimulation and/or recurrent
implantation failure (for ≥2 cycles),
(2) ovarian and/or pelvic
endometriosis, (3) raised early
follicular phase FSH (>10 IU/l)
Balk et al. [43] 57 Non-randomized—women U.S.A. TA and AA for 25 min Lying still for CPR,
receiving an ET before and after ET 25 min before and
after ET
Madaschi et al. 416 randomized—women Brazil TA No intervention CPR, IR, LBR,
[45] undergoing ICSI cycles for the first MR
time
So et al. [54] 226 randomized—women China TA Placebo needling CPR, OPR, IR,
undergoing FET treatment at the same LBR, MR
acupoints as the
real acupuncture
group
Yin et al. [55] 60 randomized—no inclusion criteria China TA, AA and Chinese No intervention CPR,
medicinal herbs
e238 F. Qu et al. / European Journal of Integrative Medicine 4 (2012) e234–e244
Table 1 (Continued)
Study Participants
Moy et al. [44] 161 randomized—women <38 years
old undergoing IVF with or without
ICSI
Cui et al. [56] 66 randomized—women with
polycystic ovary syndrome
undergoing IVF–ET
Zhang et al. [12] 309 randomized—infertile women
aged 21–44 years, eligible for ET, no
adverse ovarian reserve, no previous
acupuncture experience
Note: IVF: in vitro fertilization; ICSI: intracytoplasmic-sperm-injection; ET: embryo transfer; TVOR: time of transvaginal oocyte retrieval; EA: electro-acupuncture;
TA: traditional acupuncture; AA: auricular acupuncture; PCB: paracervical block; PCA: patient-controlled analgesia (remifentanil pump); CPR: clinical pregnancy
rate; IR: implantation rate; MR: miscarriage rate; BCPR: biochemical pregnancy rate; OPR: ongoing pregnancy rate; LBR: live birth rate; BMI: body mass index;
COH: controlled ovarian hyper-stimulation; TCM: traditional Chinese medicine; FET: frozen-thawed embryo transfer.
influence study outcome and need to be considered in future trial
design are as follows:
1. Main aim of the studies: Six studies were mainly designed to
assess the pain-relieving effects of acupuncture used at the
time of trans-vaginal oocyte retrieval (TVOR) compared
with conventional analgesia [10,23–27], while the other
studies were designed to evaluate the effects of acupuncture
on the outcomes of IVF.
2. Country of location: The studies were performed
in Germany [28–30], Denmark [12,24,27,31], Sweden
[10,23,25], Italy [32] Austria, [26], Australia [33,34],
U.S.A. [35–45], Brazil [46], China [13,47–57]. Inter-
country differences in patients’ experience, expectations
and knowledge of acupuncture may lead to variability in
outcomes.
3. Single vs. multicenter studies and variations in treatment
protocol: Among all the 38 trials reviewed, only four were
multi-center trials [10,12,23,38]. Single-center trials may
produce more inconsistent conclusions due to differences in
the protocols for IVF or ICSI, such as the protocol for con-
trolled ovarian hyperstimulation (COH), the baseline CPR
and LBR, which appeared to differ in various centers.
4. Study size: The average number of participants in the rel-
evant studies was 190 patients, with a range of 10–1000
patients. In the trials reviewed, thirteen trials provided
a power analysis and presented a calculation of sample
size [13,23–27,30,33,43,45,46,54,55]. IVF outcomes are
affected by many confounders, such as life style, gyneco-
logical and IVF associated factors. The higher the absolute
value of the correlation between the exposure and the con-
founder, the larger the sample size required [58]. Many
studies to date have not been of sufficient size to demonstrate
meaningful results.
5. Participant characteristics: Although some of the studies
described detailed inclusion criteria of the patients, for most
Country Intervention Control IVF outcomes
U.S.A. TA and AA for 25 min Placebo needling CPR, BCPR
before and after ET in non-qi lines in
the predetermined
locations. AA was
performed at the
following
acupoints: knee,
heel, allergic area,
mouth
China EA No intervention CPR
China Double EA: 24 h before Mock EA: 30 min CPR, IR, LBR
ET and 30 min after ET after ET; single
EA: 30 min after
ET
of the studies the inclusion criteria were not clearly stated.
The women’s age, body mass index (BMI) and other known
confounding factors such as number of previous IVF cycles,
duration and cause of infertility have been shown important
in large prospective studies [59,60]. Lifestyle factors such
as smoking and alcohol intake are also important and these
should be clearly described in future studies.
6. Location of acupuncture treatment provision: The location
of the acupuncture provision includes hospital, IVF center,
the acupuncturists’ offices and the patients’ home. Stress,
anxiety and depression contribute to lower pregnancy rates
among women undergoing IVF [61]. Both anxiety and
depression negatively influenced the CPR of IVF treatment
in women with tubal factor infertility [62]. When control-
ling for other factors, a strong negative relationship existed
between state anxiety and CPR of women undergoing IVF
or ICSI treatment [63].
7. Choice of controls and placebo: Control interventions
included: no intervention, lying still for a similar time as
the intervention group before and after ET, bed rest for 1 h
after ET, superficial needling of the true acupoints, placebo
needling at acupoints designed not to influence fertility,
placebo needling at acupoints close to the real acupunc-
ture acupoints and sham laser acupuncture. According to a
recent paper, researchers were advised to carefully weigh
the benefits and drawbacks of using sham acupuncture to
blind patients in adjuvant acupuncture for IVF trials, and
should question, rather than automatically accept, whether
“placebo effects” are key risk factors of bias in this con-
text [64]. Moreover, the Streitberger control may not be
an inactive control according to a recent meta-analysis [8].
Placebo needling does not make for a placebo control and
hence is best avoided [65], especially for fertility where the
outcomes are objective [64]. Including so many different
controls may have influenced the efficacy of the inter-
vention and caused variability in the measured outcomes.
Table 2
Quality evaluation of the studies.
Study Randomization Randomization method Single-/multi- Concealment Placebo Blinding Comparability at Acupuncture Adherence to
center of allocation intervention baseline practitioner STRICTA

Stener-Victorin Yes Not mentioned Multi-center Adequate No No Unclear Trained midwives No

et al. [9]
Paulus et al. [27] Yes Computerized Single-center Adequate No Yes Yes Trained examiner No
randomization
Balk et al. [34] No – Single-center None No No Unclear Not mentioned No
Paulus et al. [28] Yes Not mentioned Single-center Adequate Yes No Unclear Not mentioned No
Stener-Victorin Yes Not mentioned Multi-center Adequate No No Unclear Trained nurses Yes
et al. [22]
Zhang et al. [46] Yes Not mentioned Single-center Unclear Yes Yes Yes Not mentioned No

F. Qu et al. / European Journal of Integrative Medicine 4 (2012) e234–e244

Humaidan and Yes Not mentioned Single-center Adequate No No Yes Trained nurses Yes
Stener-Victorin
[23]
Gejervall et al. Yes Computerized Single-center Unclear No No Unclear Four midwives Yes
[24] randomization
Benson et al. [35] Yes Not mentioned Single-center Unclear No (except laser No (except laser Yes Acupuncturist No
group) groups)
Dieterle et al. [29] Yes Not mentioned Single-center Adequate Yes Yes Yes Physician No
Domar et al. [36] Yes Not mentioned Single-center Unclear No Yes Yes Not mentioned No
Humaidan et al. Yes Not mentioned Single-center Adequate No No Yes Trained nurses Yes
[26]
Sator- Yes Computerized Single-center Unclear Yes Yes Yes Trained Yes
Katzenschlager randomization gynecologist
et al. [25]
Smith et al. [32] Yes Block randomization Single-center Adequate Yes Yes Yes Acupuncturist Yes
Westergaard et al. Yes Unclear Single-center Adequate No No Yes Nurse Yes
[30]
Xu [47] Yes Not mentioned Single-center None No No Unclear Not mentioned No
Craig et al. [37] Yes Computerized Multi-center Adequate No Yes Yes Acupuncturist No
randomization
Cui et al. [48] Yes Not mentioned Single-center Unclear No No Yes Not mentioned No
Cai et al. [38] No – Single-center None No No Unclear Not mentioned No
Cui et al. [49] No – Single-center None No No Yes Acupuncturist No
Fratterelli et al. Yes Not mentioned Single-center Adequate Yes Yes Yes Acupuncturist No
[39]
Chen et al. [50] Yes Computerized Single-center Unclear No No Yes Unclear No
randomization
Chen et al. [51] Yes Not mentioned Single-center Unclear No No Yes Not mentioned No
Domar et al. [40] Yes Computerized Single-center Adequate No Yes Yes Acupuncturist No
randomization
Ho et al. [52] Yes By selection of a sealed Single-center Unclear No No Yes Not mentioned No
envelope
Kong et al. [41] Yes Not mentioned Single-center None No No Unclear Not mentioned No
Magarelli et al. No – Single-center None No No Yes Acupuncturist No
[42]
Smith et al. [33] Yes Computerized Single-center Adequate No No Yes Acupuncturist Yes
randomization

e239
So et al. [53] Yes Computerized Single-center Adequate Yes Yes Yes Acupuncturist Yes
randomization
e240 F. Qu et al. / European Journal of Integrative Medicine 4 (2012) e234–e244

Comparisons with no acupuncture intervention or with other

promising adjuvant treatments should be encouraged.
Adherence to

8. Blinding: In an acupuncture clinical trial theoreti-

STRICTA

cally blinding can include the patient, acupuncturist,

assessor, analyst and clinician. In all the studies
Yes

Yes

Yes

Yes
No
No

No

No
No
reviewed, blinding was only applied in fifteen studies
[12,13,26,28,30,33,37,38,40,41,45–47,54,55]. Although
Nurses who were

Not mentioned

Not mentioned

Not mentioned
Not mentioned
acupuncturists

blinding is problematic for the physicians or the acupunc-

Acupuncturist
Acupuncturist

Acupuncturist

Acupuncturist
Acupuncture

professional
practitioner

authorized

turists administering the acupuncture treatment, it is not

impossible, and elaborate methods are available. The
blinding should be assessed early in the study to avoid
being influenced by the outcomes of treatment, and patients
blinding should be preserved by careful attention to verbal
Comparability at

and non-verbal communication [66,67].

9. Acupuncture dose and mode of delivery: Acupuncture
baseline

Unclear
used in these studies included traditional acupuncture
Yes

Yes

Yes

Yes

Yes
Yes

Yes
No

needling, auricular acupuncture, electro-acupuncture and

laser acupuncture. Variation in the delivery, frequency and
intensity of the acupuncture may affect the results, but
in some cases there was insufficient recording of these
details. According to STRICTA criteria [22], these details
Blinding

include number of needle insertions per subject per ses-

Yes

Yes

Yes

Yes

Yes
No
No

No

No

sion (mean and range where relevant), names (or location

if no standard name) of acupoints used (uni/bilateral),
depth of insertion based on a specified unit of measure-
intervention

ment or on a particular tissue level, response sought (e.g.

de qi or muscle twitch response), needle stimulation (e.g.
Placebo

manual, electrical), needle retention time, needle type

Yes

Yes

Yes

Yes
No
No
No

No

No

(diameter, length, and manufacturer or material), number

of treatment sessions, frequency and duration of treatment
Concealment
of allocation

sessions and details of other interventions administered to

Adequate

Adequate

Adequate

Adequate
Unclear

Unclear

Unclear
Unclear

the acupuncture group (e.g. moxibustion, cupping, herbs,

None

exercises, lifestyle advice) [22]. Among the 38 included tri-

als, acupuncture was applied along with Chinese medicinal
Note: STRICTA: standards for reporting interventions in clinical trials of acupuncture.

herbs in four trials [30,39,48,56], and the combined use of

acupuncture and Chinese medicinal herbs led to better IVF
Single-/multi-

Single-center
Single-center
Single-center

Single-center

Single-center
Single-center

Single-center
Single-center
Multi-center

outcomes.
10. Acupoints selected and use of diagnostic patterns: In most
center

studies, the acupuncture protocol was developed based on

the clinical experience in practice, traditional literature and
Randomization method

consultation with experts in traditional Chinese medicine

(TCM). Neiguan (PC6), Diji (SP8), Taichong (LR3), Guilai
Not mentioned

Not mentioned

Not mentioned

(ST29), Zusanli (ST36), Sanyinjiao (SP6), and Xuehai

randomization

randomization

randomization

randomization

randomization
Computerized

Computerized

Computerized

Computerized

Computerized

(SP10) were the most frequently used acupoints. Most of

the acupoint protocols have overlapped considerably, with
a common root in one seminal RCT [28], though there was
–

some variation from study to study. In clinical practice of

Randomization

acupuncture, the acupoints are usually selected based on the

diagnosis of the patient’s syndrome according to TCM the-
ory. Among the 38 trials reviewed, only one trial [50] used
Yes

Yes

Yes

Yes

Yes
Yes

Yes
Yes
No

this method, with patients being divided into three groups,

each with a different selection of acupoints.
Table 2 (Continued)

Arnoldi et al. [31]

11. Timing of acupuncture delivery: In some of the studies,

Zhang et al. [12]
Madaschi et al.
Andersen et al.

Balk et al. [43]

Moy et al. [44]

Yin et al. [55]

Cui et al. [56]

acupuncture was applied around the time of TVOR to assess

So et al. [54]

the pain-relieving effects. In most trials, acupuncture was

[11]

[45]

applied around the time of ET. Different timing in the pro-

Study

vision of the acupuncture intervention during IVF may

 F. Qu et al. / European Journal of Integrative Medicine 4 (2012) e234–e244
account for variations in outcome and research is needed
to define the appropriate time to provide acupuncture to
maximize its effects.
12. The acupuncture practitioners: The education, training and
practice of acupuncture practitioners may influence the
nature of the acupuncture treatment given and is therefore a
variable that may significantly affect the IVF outcome. The
acupuncture practitioners in these studies included: TCM
doctors or practitioners, trained midwives, trained exam-
iners, trained nurses, physicians, traditional acupuncturists
and trained gynecologists. The duration of relevant train-
ing, length of clinical experience, and details of expertise
in treating the specific condition being evaluated, as well as
practical experience that may be relevant to the trial should
be clearly described in future studies.
13. Definition of indicators of IVF outcome: The IVF outcomes
include the indicators of CPR, BCPR, OPR, IR, LBR and
MR. For most studies, the authors failed to give the exact
definition of these outcome indicators, and in the other
studies the definition of the outcome indicators was often
different: for example, in some studies, OPR was defined
as pregnancy beyond 10 weeks of gestation, and in other
studies it was defined as pregnancy beyond 16 or 18 weeks
of gestation. The variation in the definition of IVF outcome
indicators may produce inconsistent results.
Despite the recent systematic review and meta-analysis in this
area, this is a more comprehensive review which adds new infor-
mation and is critical to direct future research. This is illustrated
as follows:
(1) STRICTA criteria [22] were used to appraise all
the included trials. However, only thirteen trials
[12,23–27,31,33,34,45,46,54,55] adhered to STRICTA.
(2) To provide a more comprehensive review, five non-
randomized trials were also included [35,39,43,44,50].
(3) Nine trials published in Chinese were included
[39,47–52,56,57], which had been omitted in the pre-
vious reviews and meta-analysis. Among these seven were
randomized controlled trials [47–49,51,52,56,57] and two
were non-randomized controlled trials [39,50]
(4) Four trials which combined the use of acupuncture and
Chinese medicinal herbs were included [30,39,48,56].
(5) One trial [50], in which, the women were divided into three
groups based on the diagnosis of the patient’s syndrome
according to TCM theories was also included.
Recommendations for the design of future studies
The limitations identified due to this clinical trial heterogene-
ity suggest a more rigorous approach is required in future studies
and this may be achieved by:
1. Conducting multi-center studies: As early as in 2006, there
was a recommendation to establish an international multicen-
ter study group to evaluate the effects of acupuncture on IVF
and ICSI outcomes [68]. Multi-center trials using the same
e241
study design may reduce the variation caused by the different
protocols for IVF or ICSI and differences in baseline CPR
and LBR observed between different centers.
2. Taking into account or stratifying according to the differ-
ent confounders which have been shown to influence IVF
outcome, which include: life style factors (maternal and
paternal age, weight, vitamin and iodine intake, alcohol and
caffeine consumption, smoking, substance misuse, stress,
environmental pollutants, oxidative stress, etc.), gynecolog-
ical factors (duration and cause of infertility, presence and
characteristics of uterine fibroids etc.), number of previ-
ous IVF cycles, presence of male factor, race and ethnicity
[60,69–71]. Some of the IVF-associated factors including
the serum levels of luteinizing hormone (LH), follicle stim-
ulating hormone (FSH), total testosterone (TT) and estradiol
(E2 ) on the 3rd day of spontaneous menstrual cycle, the cycle
length, the dosage of recombinant FSH administered, induc-
tion length, number of follicles, number of follicles with
diameters of more than 14 mm, number of embryos trans-
ferred per cycle, embryo cleavage rate, good-quality embryo
rate and fertilization rate have been shown to have impor-
tant influence on IVF outcomes in large prospective studies
[59,60,72].
3. Using the STRICTA criteria to make protocols reproducible
[22]. The revised STRICTA includes 6 items and 17 sub-
items, which set the reporting guidelines for the acupuncture
rationale, the details of needling, the treatment regimen, other
components of treatment, the practitioner background, and
the control or comparator intervention [73]. STRICTA has
provided authors a way to structure their reports of interven-
tions with a minimum set of items within a checklist and
should be used as the gold standard not only in reporting the
trials, but in designing the whole study. One area that is often
inadequately reported is a precise description of the control
intervention, including needling details and regimen if these
are different from those used in the acupuncture group. Some
potential factors may influence the applicability of “placebo”
needling, amongst which the patient’s knowledge, expec-
tation and experience of acupuncture, acupuncture point
selection and the visual impact of needling are the most
important [74].
4. Establishing detailed fixed protocols based on the correct
diagnosis of the patient’s syndrome according to TCM the-
ories and expert opinion. As an important part of TCM,
acupuncture is based on the classical theories of TCM.
The effects of acupuncture on IVF or ICSI outcomes
would be predicted to improve with the correct diagno-
sis of the patient’s syndrome based on TCM theories; also
the outcomes may vary according to which syndromes are
predominant. Some key factors of acupuncture treatment
including the angle/direction of insertion, the manipula-
tion method (thrusting, lifting, and rotating techniques)
and intensity of these manipulation methods are based
on the TCM diagnosis, and hence may vary for differ-
ent IVF patients. Consequently, the detailed fixed protocols
should be based on the correct diagnosis of the patient’s
syndrome [75,76].
e242 F. Qu et al. / European Journal of Integrative Medicine 4 (2012) e234–e244
5. Providing a sufficient dose of treatment over the most appro-
priate time period. Most trials to date have given only two
acupuncture treatments, one either side of ET. Only a few
have been around TVOR but their primary aim has been
analgesia rather than fertility treatment [27,53]. Some have
also provided adjunctive acupuncture before or during the
earlier ovarian hyper-stimulation phase [49,51,52]. This last
approach would appear to be more comparable to TCM
theory and practice, though there is currently no research
information to inform this aspect of the protocol.
6. Calculating adequate sample sizes. As with any clinical trial,
the sample size should be calculated based on previous
research and take into account the effect of confounders.
7. Using all the relevant indicators of IVF outcome in future
studies. Although over forty clinical trials have been pub-
lished, due to the complexity of acupuncture and the unknown
mechanism, more indicators should be explored. Besides the
commonly used indicators for IVF outcomes, such as CPR,
BCPR, OPR, IR, LBR and MR, some further relevant indi-
cators should also be considered, such as fertilization rate,
embryo cleavage rate, good-quality embryo rate and inci-
dence of birth defects. Also the general wellbeing of the
mother and the birth of a healthy baby are important indi-
cators.
It is hoped that these recommendations will provide useful
guidelines for promoting better trial design and hence improve
the evidence base for the use of acupuncture for IVF.
Author’s contribution
Fan Qu contributed to conception and design of the study,
acquisition of data, analysis and interpretation of data; con-
tributed to draft the article and revise it critically for important
intellectual content; and approved the version to be published.
Jue Zhou contributed to conception and design of the study,
acquisition of data, analysis and interpretation of data; con-
tributed to draft the article and revise it critically for important
intellectual content; and approved the version to be published.
Mark Bovey contributed to acquisition of data, analysis and
interpretation of data; contributed to draft the article and revise
it critically for important intellectual content; and approved
the version to be published. Giovanna Franconi contributed
to analysis and interpretation of data; contributed to revise
the manuscript critically for important intellectual content; and
approved the version to be published. Kelvin Chan contributed
to analysis and interpretation of data; contributed to revise
the manuscript critically for important intellectual content; and
approved the version to be published. Caroline Smith con-
tributed to analysis and interpretation of data; contributed to
revise the manuscript critically for important intellectual con-
tent; and approved the version to be published. Dan Jiang
contributed to analysis and interpretation of data; contributed
to revise the manuscript critically for important intellectual con-
tent; and approved the version to be published. Nicola Robinson
contributed to conception and design of the study, acquisition of
data, analysis and interpretation of data; contributed to draft the
article and revise it critically for important intellectual content;
and approved the version to be published.
Funding
This work was supported by Good Practice in Traditional Chi-
nese Medicine Research in the Post-genomic Era (GP-TCM),
a Coordination Action funded by the European Union’s 7th
Framework Program under the grant agreement No. 223154.
Conflict of interest
No competing financial interests exist.
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